tbuckley/cabot-search huggingface dataset:
Antiviral CD8<sup>+</sup>T-cell immune responses are impaired by cigarette smoke and in COPD
Authors: Jie Chen, Xinyuan Wang, Adrian Schmalen, Sophia Haines, Martin Wolff, Huan Ma, Huabin Zhang, Mircea Gabriel Stoleriu, Johannes Nowak, Misako Nakayama, Marta Bueno, Judith Brands, Ana L. Mora, Janet S. Lee, Susanne Krauss-Etschmann, Anna Dmitrieva, Marion Frankenberger, Thomas P. Hofer, Elfriede Noessner, Andreas Moosmann, Jürgen Behr, Katrin Milger, Cornelia A. Deeg, Claudia A. Staab-Weijnitz, Stefanie M. Hauck, Heiko Adler, Torsten Goldmann, Karoline I. Gaede, Jochen Behrends, Ilona E. Kammerl, Silke Meiners
Journal: European Respiratory Journal (2023)

Background Virus infections drive COPD exacerbations and progression. Antiviral immunity centres on the activation of virus-specific CD8 + T-cells by viral epitopes presented on major histocompatibility complex (MHC) class I molecules of infected cells. These epitopes are generated by the immunoproteasome, a specialised intracellular protein degradation machine, which is induced by antiviral cytokines in infected cells. Methods We analysed the effects of cigarette smoke on cytokine- and virus-mediated induction of the immunoproteasome in vitro , ex vivo and in vivo using RNA and Western blot analyses. CD8 + T-cell activation was determined in co-culture assays with cigarette smoke-exposed influenza A virus (IAV)-infected cells. Mass-spectrometry-based analysis of MHC class I-bound peptides uncovered the effects of cigarette smoke on inflammatory antigen presentation in lung cells. IAV-specific CD8 + T-cell numbers were determined in patients’ peripheral blood using tetramer technology. Results Cigarette smoke impaired the induction of the immunoproteasome by cytokine signalling and viral infection in lung cells in vitro , ex vivo and in vivo . In addition, cigarette smoke altered the peptide repertoire of antigens presented on MHC class I molecules under inflammatory conditions. Importantly, MHC class I-mediated activation of IAV-specific CD8 + T-cells was dampened by cigarette smoke. COPD patients exhibited reduced numbers of circulating IAV-specific CD8 + T-cells compared to healthy controls and asthmatics. Conclusion Our data indicate that cigarette smoke interferes with MHC class I antigen generation and presentation and thereby contributes to impaired activation of CD8 + T-cells upon virus infection. This adds important mechanistic insight on how cigarette smoke mediates increased susceptibility of smokers and COPD patients to viral infections.
Implementation and evaluation of ultra-low dose CT in early cystic fibrosis lung disease
Authors: Katie J. Bayfield, Oliver Weinheimer, Christie Boyton, Rachel Fitzpatrick, Anna Middleton, Brendan Kennedy, Anneliese Blaxland, Geshani Jayasuriya, Neil Caplain, Hana Issa, Robert Goetti, Mark O. Wielpütz, Lifeng Yu, Craig J. Galban, Terry E. Robinson, Brian Bartholmai, Dominic Fitzgerald, Hiran Selvadurai, Paul D. Robinson
Journal: European Respiratory Journal (2023)

Optimal characterisation of early structural abnormalities has been highlighted as critical to future efforts to detect and prevent cystic fibrosis (CF) lung disease progression [1]. CT is currently the gold standard, detecting structural disease at an earlier stage than x-ray or lung function testing, with predictive value for subsequent progression and later FEV1 decline [1]. Compared to other emerging radiological modalities for early disease detection, such as MRI, CT is more widely accessible and MRI at present is not able to directly quantify the extent of bronchiectasis due to its limitations in spatial resolution. Current US CF foundation clinical guidelines state that CT should be "considered every 2–3 years, using the lowest possible radiation dose". Early lung disease is identified on CT by air trapping, increase in airway wall thickness and airway diameter, and potentially irreversible bronchiectasis [2]. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: The authors have nothing to disclose.
Airway smooth muscle area to predict steroid responsiveness in COPD patients receiving triple therapy (HISTORIC): a randomised, placebo-controlled, double-blind, investigator-initiated trial
Authors: Daiana Stolz, Eleni Papakonstantinou, Maria Pascarella, Kathleen Jahn, Aline Siebeneichler, Andrei M. Darie, Matthias J. Herrmann, Werner Strobel, Anna Salina, Leticia Grize, Spasenija Savic Prince, Michael Tamm
Journal: European Respiratory Journal (2023)

Background Although inhaled corticosteroids (ICS) are highly effective in asthma, they provide significant, but modest, clinical benefit in COPD. Here, we tested the hypothesis that high bronchial airway smooth muscle cell (ASMC) area in COPD is associated with ICS responsiveness. Methods In this investigator-initiated and -driven, double-blind, randomised, placebo-controlled trial (HISTORIC), 190 COPD patients, Global Initiative for Chronic Obstructive Lung Disease stage B–D, underwent bronchoscopy with endobronchial biopsy. Patients were divided into groups A and B, with high ASMC area (HASMC: &gt;20% of the bronchial tissue area) and low ASMC area (LASMC: ≤20% of the bronchial tissue area), respectively, and followed a run-in period of 6 weeks on open-label triple inhaled therapy with aclidinium (ACL)/formoterol (FOR)/budesonide (BUD) (400/12/400 μg twice daily). Subsequently, patients were randomised to receive either ACL/FOR/BUD or ACL/FOR/placebo and followed for 12 months. The primary end-point of the study was the difference in post-bronchodilator forced expiratory volume in 1 s (FEV 1 ) over 12 months between patients with LASMC and HASMC receiving or not receiving ICS. Results In patients with LASMC, ACL/FOR/BUD did not significantly improve FEV 1 over 12 months, as compared to ACL/FOR/placebo (p=0.675). However, in patients with HASMC, ACL/FOR/BUD significantly improved FEV 1 , as compared to ACL/FOR/placebo (p=0.020). Over 12 months, the difference of FEV 1 change between the ACL/FOR/BUD group and the ACL/FOR/placebo group was 50.6 mL·year −1 within the group of patients with LASMC and 183.0 mL·year −1 within the group of patients with HASMC. Conclusion COPD patients with ΗASMC respond better to ICS than patients with LASMC, suggesting that this type of histological analysis may predict ICS responsiveness in COPD patients receiving triple therapy.
Quantifying COPD as a risk factor for cardiac disease in a primary prevention cohort
Authors: Laura C. Maclagan, Ruth Croxford, Anna Chu, Don D. Sin, Jacob A. Udell, Douglas S. Lee, Peter C. Austin, Andrea S. Gershon
Journal: European Respiratory Journal (2023)

Despite COPD being a risk factor for cardiovascular disease (CVD) and knowing that risk stratification for CVD primary prevention is important, little is known about the real-world risk of CVD among people with COPD with no history of CVD. This knowledge would inform CVD management for people with COPD. The current study aimed to examine the risk of major adverse cardiovascular events (MACE) (including acute myocardial infarction, stroke or cardiovascular death) in a large, complete real-world population with COPD without previous CVD.We conducted a retrospective population cohort study using health administrative, medication, laboratory, electronic medical record and other data from Ontario, Canada. People without a history of CVD with and without physician-diagnosed COPD were followed between 2008 and 2016, and cardiac risk factors and comorbidities compared. Sequential cause-specific hazard models adjusting for these factors determined the risk of MACE in people with COPD.Among ∼5.8 million individuals in Ontario aged ≥40 years without CVD, 152 125 had COPD. After adjustment for cardiovascular risk factors, comorbidities and other variables, the rate of MACE was 25% higher in persons with COPD compared with those without COPD (hazard ratio 1.25, 95% CI 1.23-1.27).In a large real-world population without CVD, people with physician-diagnosed COPD were 25% more likely to have a major CVD event, after adjustment for CVD risk and other factors. This rate is comparable to the rate in people with diabetes and calls for more aggressive CVD primary prevention in the COPD population.
Align with the NMIND consortium for better neuroimaging
Authors: Gregory Kiar, Jon Clucas, Eric Feczko, Mathias Goncalves, Dorota Jarecka, Christopher J. Markiewicz, Yaroslav O. Halchenko, Robert Hermosillo, Xinhui Li, Oscar Miranda-Dominguez, Satrajit Ghosh, Russell A. Poldrack, Theodore D. Satterthwaite, Michael P. Milham, Damien Fair
Journal: Nature Human Behaviour (2023)
Understanding and combatting misinformation across 16 countries on six continents
Authors: Antonio A. Arechar, Jennifer Allen, Adam J. Berinsky, Rocky Cole, Ziv Epstein, Kiran Garimella, Andrew Gully, Jackson G. Lu, Robert M. Ross, Michael N. Stagnaro, Yunhao Zhang, Gordon Pennycook, David G. Rand
Journal: Nature Human Behaviour (2023)
Abemaciclib Is Effective in Palbociclib-Resistant Hormone Receptor–Positive Metastatic Breast Cancers
Authors: Juliana Navarro-Yepes, Nicole M. Kettner, Xiayu Rao, Cassandra Santaella Bishop, Tuyen N. Bui, Hannah F. Wingate, Akshara Singareeka Raghavendra, Yan Wang, Jing Wang, Aysegul A. Sahin, Funda Meric-Bernstam, Kelly K. Hunt, Senthil Damodaran, Debu Tripathy, Khandan Keyomarsi
Journal: Cancer Research (2023)

Cyclin-dependent kinases 4/6 inhibitor (CDK4/6i) plus endocrine therapy (ET) is standard of care for patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (MBC). However, resistance to CDK4/6is plus ET remains a clinical problem with limited therapeutic options following disease progression. Different CDK4/6is might have distinct mechanisms of resistance, and therefore using them sequentially or targeting their differentially altered pathways could delay disease progression. To understand pathways leading to resistance to the CDK4/6is palbociclib and abemaciclib, we generated multiple in vitro models of palbociclib-resistant (PR) and abemaciclib-resistant (AR) cell lines as well as in vivo patient-derived xenografts (PDX) and ex vivo PDX-derived organoids (PDxO) from patients who progressed on CDK4/6i. PR and AR breast cancer cells exhibited distinct transcriptomic and proteomic profiles that sensitized them to different classes of inhibitors; PR cells upregulated G2-M pathways and responded to abemaciclib, while AR cells upregulated mediators of the oxidative phosphorylation pathway (OXPHOS) and responded to OXPHOS inhibitors. PDX and organoid models derived from patients with PR breast cancer remained responsive to abemaciclib. Resistance to palbociclib while maintaining sensitivity to abemaciclib was associated with pathway-specific transcriptional activity but was not associated with any individual genetic alterations. Finally, data from a cohort of 52 patients indicated that patients with HR-positive/HER2-negative MBC who progressed on palbociclib-containing regimens can exhibit a meaningful overall clinical benefit from abemaciclib-based therapy when administered after palbociclib. These findings provide the rationale for clinical trials evaluating the benefit of abemaciclib treatment following progression on a prior CDK4/6i.
Cortical somatostatin interneuron subtypes form cell-type-specific circuits
Authors: Sherry Jingjing Wu, Elaine Sevier, Deepanjali Dwivedi, Giuseppe-Antonio Saldi, Ariel Hairston, Sabrina Yu, Lydia Abbott, Da Hae Choi, Mia Sherer, Yanjie Qiu, Ashwini Shinde, Mackenzie Lenahan, Daniella Rizzo, Qing Xu, Irving Barrera, Vipin Kumar, Giovanni Marrero, Alvar Prönneke, Shuhan Huang, Klas Kullander, David A. Stafford, Evan Macosko, Fei Chen, Bernardo Rudy, Gord Fishell
Journal: Neuron (2023)
The association between zinc deficiency, and clinical outcomes of COVID-19
Authors: Jheng-Yan Wu, Wan-Hsuan Hsu, Ya-Wen Tsai, Ting-Hui Liu, Po-Yu Huang, Min-Hsiang Chuang, Szu-En Chin, Chih-Cheng Lai, Mei-Yuan Liu
Journal: Journal of Infection (2023)
Dually fibronectin/CD44-mediated nanoparticles targeted disrupt the Golgi apparatus and inhibit the hedgehog signaling in activated hepatic stellate cells to alleviate liver fibrosis
Authors: Yanping Li, Ting Zhang, Jinhang Zhang, Qinhui Liu, Qingyi Jia, Wenfei Chen, Qin Tang, Yimin Xiong, Yan Xia, Ying Xu, Li Mo, Yuan Huang, Jinhan He
Journal: Biomaterials (2023)
Imprinting disorders
Authors: Thomas Eggermann, David Monk, Guiomar Perez de Nanclares, Masayo Kagami, Eloïse Giabicani, Andrea Riccio, Zeynep Tümer, Jennifer M. Kalish, Maithé Tauber, Jessica Duis, Rosanna Weksberg, Eamonn R. Maher, Matthias Begemann, Miriam Elbracht
Journal: Nature Reviews Disease Primers (2023)
An aggregation of aggregation methods in computational pathology
Authors: Mohsin Bilal, Robert Jewsbury, Ruoyu Wang, Hammam M. AlGhamdi, Amina Asif, Mark Eastwood, Nasir Rajpoot
Journal: Medical Image Analysis (2023)

Image analysis and machine learning algorithms operating on multi-gigapixel whole-slide images (WSIs) often process a large number of tiles (sub-images) and require aggregating predictions from the tiles in order to predict WSI-level labels. In this paper, we present a review of existing literature on various types of aggregation methods with a view to help guide future research in the area of computational pathology (CPath). We propose a general CPath workflow with three pathways that consider multiple levels and types of data and the nature of computation to analyse WSIs for predictive modelling. We categorize aggregation methods according to the context and representation of the data, features of computational modules and CPath use cases. We compare and contrast different methods based on the principle of multiple instance learning, perhaps the most commonly used aggregation method, covering a wide range of CPath literature. To provide a fair comparison, we consider a specific WSI-level prediction task and compare various aggregation methods for that task. Finally, we conclude with a list of objectives and desirable attributes of aggregation methods in general, pros and cons of the various approaches, some recommendations and possible future directions.
Transforming clinical research and science in bronchiectasis: EMBARC3, a European Respiratory Society Clinical Research Collaboration
Authors: James D. Chalmers, Stefano Aliberti, Josje Altenburg, Francesco Blasi, Clare Clarke, Sanjay H. Chotirmall, Megan L. Crichton, Raja Dhar, Pieter Goeminne, Charles Haworth, Michael R. Loebinger, Natalie Lorent, Eva Polverino, Felix C. Ringshausen, Amelia Shoemark, Michal Shteinberg, Oriol Sibila, Arietta Spinou, Tobias Welte
Journal: European Respiratory Journal (2023)

Bronchiectasis is a major health problem that is increasing in prevalence and burden globally [1, 2]. The impact of bronchiectasis on patients and the healthcare system is exacerbated by the decades in which the disease was under-recognised, under-researched and poorly treated [3]. There remain no treatments licensed by regulatory authorities worldwide, and many of the treatments that are used in routine clinical practice lack robust evidence [4]. Therapeutic development in bronchiectasis is undermined by the lack of experimental models and a lack of fundamental understanding of the disease. This makes bronchiectasis less attractive for investment into new therapeutic research compared to other fields. EMBARC3 is a programme of clinical and translational research aiming to improve our understanding of bronchiectasis globally <https://bit.ly/42n3HD8> We thank Celine Genton and Elise Heuvelin from the European Respiratory Society (Lausanne, Switzerland) for logistical support.
Inhaled treprostinil for interstitial lung disease-associated pulmonary hypertension: a silver lining on a very dark cloud
Authors: Vincent Cottin, Claudia Valenzuela, Marc Humbert
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>Pulmonary hypertension associated with ILD is a very severe condition. The open label extension of the INCREASE trial demonstrates acceptable tolerability of inhaled treprostinil, maintained exercise capacity at week 40, and increase in FVC.</b>https://bit.ly/3qxHvsB
Social regulation of reproduction: control or signal?
Authors: Chiara Benvenuto, Maria Cristina Lorenzi
Journal: Trends in Ecology & Evolution (2023)

Traditionally, dominant breeders have been considered to be able to control the reproduction of other individuals in multimember groups that have high variance in reproductive success/reproductive skew (e.g., forced sterility/coercion of conspecifics in eusocial animals; sex-change suppression in sequential hermaphrodites). These actions are typically presented as active impositions by reproductively dominant individuals. However, how can individuals regulate the reproductive physiology of others? Alternatively, all contestants make reproductive decisions, and less successful individuals self-downregulate reproduction in the presence of dominant breeders. Shifting perspective from a top-down manipulation to a broader view, which includes all contenders, and using a multitaxon approach, we propose a unifying framework for the resolution of reproductive skew conflicts based on signalling rather than control, along a continuum of levels of strategic regulation of reproduction.
The reconfiguration pattern of individual brain metabolic connectome for Parkinson's disease identification
Authors: Weikai Li, Yongxiang Tang, Liling Peng, Zhengxia Wang, Shuo Hu, Xin Gao
Journal: MedComm (2023)

Abstract 18 F‐Fluorodeoxyglucose positron emission tomography ( 18 F‐FDG PET) is widely employed to reveal metabolic abnormalities linked to Parkinson's disease (PD) at a systemic level. However, the individual metabolic connectome details with PD based on 18 F‐FDG PET remain largely unknown. To alleviate this issue, we derived a novel brain network estimation method for individual metabolic connectome, that is, Jensen‐Shannon Divergence Similarity Estimation (JSSE). Further, intergroup difference between the individual's metabolic brain network and its global/local graph metrics was analyzed to investigate the metabolic connectome's alterations. To further improve the PD diagnosis performance, multiple kernel support vector machine (MKSVM) is conducted for identifying PD from normal control (NC), which combines both topological metrics and connection. Resultantly, PD individuals showed higher nodal topological properties (including assortativity, modularity score, and characteristic path length) than NC individuals, whereas global efficiency and synchronization were lower. Moreover, 45 most significant connections were affected. Further, consensus connections in occipital, parietal, and frontal regions were decrease in PD while increase in subcortical, temporal, and prefrontal regions. The abnormal metabolic network measurements depicted an ideal classification in identifying PD of NC with an accuracy up to 91.84%. The JSSE method identified the individual‐level metabolic connectome of 18 F‐FDG PET, providing more dimensional and systematic mechanism insights for PD.
Evaluating relapse-free survival as an endpoint for overall survival in adjuvant immunotherapy trials
Authors: Yuanfang Li, Shuqiang Yuan, Yingbo Chen, Man Nie, Jibin Li, Guoming Chen, Xiaojiang Chen, Ruopeng Zhang, Ziqi Zheng, Chengzhi Wei, Zhiwei Zhou, Runcong Nie, Yun Wang
Journal: JNCI Journal of the National Cancer Institute (2023)

Relapse-free survival (RFS) has been considered a primary endpoint to assess the effects of immunotherapy in the adjuvant setting among patients with early-stage disease. However, it is not clear whether RFS is a valid surrogate endpoint for overall survival (OS) in this clinical context.Phase II or III clinical trials of adjuvant immunotherapy that reported hazard ratios on OS and RFS were identified. We used a weighted regression analysis at the arm and trial levels to assess the efficacy of RFS as a surrogate for OS, quantified by the weighted coefficient of determination (R2). Strong correlations (R2 ≥ 0.7) at the arm and trial levels indicated valid surrogacy. The surrogate threshold effect was also evaluated.Fifteen high-quality randomized clinical trials involving 13 715 patients were included. At the arm level, moderate and strong associations were observed between RFS2-year and OS3-year (R2 = 0.58, 95% confidence interval [CI] = 0.25 to 0.92) and RFS3-year and OS5-year (R2 = 0.72, 95% CI = 0.38 to 1.00), respectively. At the trial level, a moderate association was observed between effect of treatment on RFS and OS (R2 = 0.63, 95% CI = 0.33 to 0.94). The surrogate threshold effect for RFS was 0.86. Consistent results were confirmed in several sensitivity analyses based on different trial phases, experimental arms, cancer types, and treatment strategies.Our meta-analysis failed to find a clinically strong association between RFS and OS in randomized clinical trials of adjuvant immunotherapy. Our findings challenge the use of RFS as the primary efficacy endpoint and suggest the use of OS in this clinical context.
High-grade cervical squamous intraepithelial lesions in female partners of men with high-grade penile squamous intraepithelial lesions: a monocentric retrospective study
Authors: Camille Isnard, Johan Chanal, Christine  Bergeron, Olivier Aynaud
Journal: British Journal of Dermatology (2023)

We have conducted the first study to focus on the presence of cervical human papillomavirus (HPV) lesions in the female partners of males with high-grade penile squamous intraepithelial lesions (PHSILs). A histologically confirmed cervical squamous intraepithelial lesion (SIL) in female partners was observed in 81% of cases, with high-grade SIL seen in more than two-thirds of cases and low-grade SIL in a third. It is important to screen females whose male partners have PHSIL, in order to detect a clinical HPV lesion early and treat it, if necessary. Our results indicate that a HPV test and reflex cytology (if the HPV test is positive) are necessary for the female partners of males with PHSIL. If there is an abnormal Pap smear, colposcopy should be performed.
Effect on life expectancy of temporal sequence in a multimorbidity cluster of psychosis, diabetes, and congestive heart failure among 1·7 million individuals in Wales with 20-year follow-up: a retrospective cohort study using linked data
Authors: Rhiannon K Owen, Jane Lyons, Ashley Akbari, Bruce Guthrie, Utkarsh Agrawal, Daniel C Alexander, Amaya Azcoaga-Lorenzo, Anthony J Brookes, Spiros Denaxas, Carol Dezateux, Adeniyi Francis Fagbamigbe, Gill Harper, Paul D W Kirk, Eda Bilici Özyiğit, Sylvia Richardson, Sophie Staniszewska, Colin McCowan, Ronan A Lyons, Keith R Abrams
Journal: The Lancet Public Health (2023)

To inform targeted public health strategies, it is crucial to understand how coexisting diseases develop over time and their associated impacts on patient outcomes and health-care resources. This study aimed to examine how psychosis, diabetes, and congestive heart failure, in a cluster of physical-mental health multimorbidity, develop and coexist over time, and to assess the associated effects of different temporal sequences of these diseases on life expectancy in Wales.
The health impact of Scotland's Baby Box Scheme: a natural experiment evaluation using national linked health data
Authors: Ronan McCabe, Srinivasa Vittal Katikireddi, Ruth Dundas, Peter Craig
Journal: The Lancet Public Health (2023)

Scotland's Baby Box Scheme (SBBS) is a national programme offering a box of essential items to all pregnant women in Scotland intended to improve infant and maternal health. We aimed to evaluate the effect of SBBS on selected infant and maternal health outcomes at population and subgroup levels (maternal age and area deprivation).